Gene therapy represents the technology by which human genes are transferred to target cells thus modifying the genetic composition of the targets. In regards to the lung, two strategies are being employed to utilize this technology to treat human lung disorders. First, adenovirus-based replication deficient recombinant vectors are being used to directly transfer genes to the respiratory epithelium in vivo. This has been accomplished with the human genes representing the two major lethal hereditary disorders in the United States and Europe, cystic fibrosis and alphal-antitrypsin deficiency. Although safety aspects of this strategy for the therapy of these disorders will have to be demon- strated, the results are encouraging breakthroughs in the design of approaches to the ultimate 'cure' of these disorders. Second, lymphocytes have been modified in vitro using retrovirus-based recombinant vectors and then transplanted to the lungs of experimental animals. The modified lymphocytes remain within the lung for at least one week and will secrete human protein as exemplified by lymphocytes modified with the human alphal-antitrypsin gene. This strategy should be useful for "organ specific" gene therapy using lymphocytes as cell targets.